The objective of this project is to develop intraoral controlled-release therapeutic systems for antibiotics/antimicrobial and antifungal agents for the treatment of periodontal disease, AIDS-related oral diseases and other opportunistic oral mycotic infections. Initial investigations focused on determining the feasibility of utilizing biocompatible copolymers of hydroxyethyl methacrylate (MEMA) and methyl methacrylate (MMA) to produce a membrane-controlled delivery system for tetracyline that could be used for short-term intraoral therapy of periodontal disease. Prototype controlled-release tetracyline pellets (TCRP's) have been produced that are discs approximately 5 mm in diameter and 2 mm thick and release approximately 0.4 to 1 mg of tetracyline per day for up to 14 days. The TCRP is composed of an inner core or reservoir that consists of tetracycline mixed with a HEMA:MMA copolymer. The core is covered by a HEMA:MMA membrane that regulates the rate at which tetracycline is released from the pellet. The polymers used are also currently being used in a fluoride-releasing pellet that is being developed by the NIDR for providing topical fluoride for the prevention of dental decay. The polymers have proven to be very biocompatible. A short-term trial of the TCRP in monkeys where the pellets were direct-bonded to anterior teeth produced favorable changes in the subgingival bacterial flora. Saliva samples collected during this experiment will be analyzed by HPLC to estimate intraoral tetracyline concentrations. Preliminary studies indicate that the copolymers also can be used to make controlled-release pellets for chlorhexidine and antifungal agents.